TESK1

protein-coding

testis associated actin remodelling kinase 1, the group of MicroRNA protein coding host genes|LIMK/TESK kinase family

Gene summary

This gene product is a serine/threonine protein kinase that contains an N-terminal protein kinase domain and a C-terminal proline-rich domain. Its protein kinase domain is most closely related to those of the LIM motif-containing protein kinases (LIMKs). The encoded protein can phosphorylate myelin basic protein and histone in vitro. The testicular germ cell-specific expression and developmental pattern of expression of the mouse gene suggests that this gene plays an important role at and after the meiotic phase of spermatogenesis. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Dec 2015]

MANE transcript

NM_006285.3

Inheritance

—

ClinVar variants

U:90B:3

Top phenotype

EBV-positive nodal T- and NK-cell lymphoma

gnomAD constraint

pLI —, LoF o/e 0.11

Max pathogenic AF

—

Genomic locus

chr9:35,605,262-35,610,041

External References & Databases

Ensembl (ENSG00000107140)

Transcript & Mutation Effects

hg38 • Region Span ~4.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TESK1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 82

EBV-positive nodal T- and NK-cell lymphomaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006285.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar			2
missense			84 clinvar	2 clinvar		86
nonsense				1 clinvar		1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	90	3	0	93

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 12 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006285.3	RefSeq	NP_006276.2	10	MANE Select
ENST00000336395.6	Ensembl	ENSP00000338127.5	10	MANE Select
NM_001318230.2	RefSeq	NP_001305159.1	6	Standard
ENST00000970553.1	Ensembl	ENSP00000640612.1	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Regulation of cytoskeletal remodeling and cell spreading by IPP complex components
Cell-extracellular matrix interactions
Cell junction organization
Cell-Cell communication

Biological Process

spermatogenesis
peptidyl-tyrosine phosphorylation
actin cytoskeleton organization
negative regulation of protein autophosphorylation
regulation of protein localization

Molecular Function

protein serine/threonine kinase activity
protein serine/threonine/tyrosine kinase activity
protein tyrosine kinase activity
protein binding
ATP binding

Cellular Component

nucleus
cytoplasm
cytosol
cytoplasmic vesicle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000336395
Coding exons: 10
Length: 4672
Individuals with no LoFs: 125734
Homozygous LoFs: 0
Heterozygous LoFs: 10
Defined: 125744
p: 0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.61	291	379	0.768	0.0000230	3931
Missense (PolyPhen)		62	141.64	0.43774		1485
Synonymous	0.819	147	160	0.918	0.00000941	1449
Loss of Function	4.36	3	27.9	0.108	0.00000177	268

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000059	0.000058	rare
Ashkenazi Jewish	0.00011	0.000099	rare
East Asian	0	0.0	absent
Finnish	0.000093	0.000092	rare
European (Non-Finnish)	0.000045	0.000044	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Dual specificity protein kinase activity catalyzing autophosphorylation and phosphorylation of exogenous substrates on both serine/threonine and tyrosine residues. Probably plays a central role at and after the meiotic phase of spermatogenesis (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.130

Intolerance Scores

LoFtool: 0.142
RVIS EVS: -0.38
RVIS percentile EVS: 27.88

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.606

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium